Patent CA-2206776-A1 (CA)
Title: N-sulfonylindoline derivatives carrying an amide functional group, their preparation and the pharmaceutical compositions in which they are present
Inventor: TONNERRE BERNARD
IPC: C07D295/192
Filed: 1992-07-31
Abstract: Compounds of formula (6):                         6 in which A' is NR6R7; -     R1 is a halogen atom, a C1-C4 alkyl, a hydroxyl, a C1-C4 alkoxy, a benzyloxy group, a cyano group, a trifluoromethyl group, nitro group or an amino group; -     R2 is a C1-C6 alkyl, a C3-C7 cycloalkyl, a C5-C7 cycloalkene or a phenyl which is unsubstituted or monosubstituted or polysubstituted by a C1-C4 alkyl, a C1-C4 alkoxy, a halogen, a trifluoromethyl group or an amino group, or R2 is a nitrophenyl which is unsubstituted or monosubstituted by a trifluoromethyl group or monosubstituted or polysubstituted by a C1-C4 alkyl, a C1-C4 alkoxy or a halogen; -    R5 is a C1-C4 alkyl; a 1-naphthyl; a 2-naphthyl; a 5-dimethylamino-1-naphthyl; a phenyl which is unsubstituted or substituted by one or more substituents selected from a halogen atom, a C1-C4 alkyl, a trifluoromethyl group, an amino group which is free or substituted by one or two C1-C4 alkyls, a hydroxyl, a C1-C4 alkoxy, a C2-C4 alkenoxy, a C1-C4 alkylthio, a trifluoromethoxy group, a benzyloxy group, a cyano group, a carboxyl group, a C1-C4 alkoxycarbonyl group, a carbamoyl group which is free or substituted by one or two C1-C4 alkyls or a  C1-C4 alkylamido group, or R5 is a nitrophenyl which is unsubstituted or monosubstituted by a trifluoromethyl group or a C2-C4 alkenoxy or mono- or polysubstituted by a halogen, a C1-C4 alkyl, a C1-C4 alkoxy, a C1-C4 alkylthio, a trifluoromethoxy group or a benzyloxy group; -  R6 is a C1-C6 alkyl or R6 is identical to R7; -  R7 is a 4-piperidyl group or a 3-azetidinyl group, the said groups being substituted or unsubstituted on the nitrogen by a C1-C4 alkyl, by a benzyloxycarbonyl or by a C1-C4 alkoxycarbonyl; a group (CH2)r which is itself substituted by a 2-, 3- or 4-pyridyl group, by a hydroxyl group or by an amino group which is free or substituted by one or two C1-C4 alkyls, a carboxyl group, a C1-C4 alkoxycarbonyl group, a benzyloxycarbonyl group or a carbamoyl group which is free or substituted by one or two C1-C4 alkyls; -  or R6 and R7 together, with the nitrogen atom to which they are connected, form a heterocycle selected from: .  morpholine, .  thiomorpholine, .  thiazolidine or 2,2-dimethylthiazolidine, unsubstituted or substituted by R8, .  piperazine, unsubstituted or substituted at the 4-position by a group R"8, .  an unsaturated, a 5-membered ring containing a single nitrogen atom and substituted by R8 or a saturated, 3-, 4-, 5-, 6- or 7-membered ring containing a single nitrogen atom and substituted by R8 and R9; -   R8 is R'8 or a group (CH2)r which is itself substituted by a hydroxyl or by an amino which is free or substituted by one or two C1-C4 alkyls;     -     R'8 is a group (CH2)q which is itself substituted by a carboxyl group, a C1-C4 alkoxycarbonyl group, a benzyloxycarbonyl group, a carbamoyl group which is free or substituted by a hydroxyl or by one or two C1-C4 alkyls or an aminocarbothioyl group which is free or substituted by one or two C1-C4 alkyls; -    R"8 is R'8 or a group (CH2)2NH2 which is free or substituted by one or two C1-C4 alkyls; -    R9 is hydrogen, a halogen, a group (CH2) rOR10, a group (CH2)rNR11R12, a group (CH2)sCONR11R'11 or an azido group; -   R10 is hydrogen, a C1-C4 alkyl, a mesyl or a tosyl; -    R11, R'11 and R12 are each a hydrogen or a C1-C4 alkyl or R11 is hydrogen and R12 is a benzyloxycarbonyl or a C1-C4 alkoxycarbonyl; -    n is 0, 1 or 2; -    m is 0, 1 or 2; -    q is 0, 1, 2 or 3; -    r is 0, 1, 2 or 3, with the limitation that r is not zero when R8 or R9 is at the alpha-position of the intracyclic amide nitrogen; -    s is  0 or 1;  are useful as intermediates of the preparation of N-sulfonylindoline derivatives which are useful in the treatment of complaints of the central nervous system, the cardiovascular system and the gastric sphere in humans and animals.